Mosdepth: quick coverage calculation for genomes and exomes

Pedersen, Brent S.; Quinlan, Aaron R.

doi:10.1093/bioinformatics/btx699

Cited by 834 publications

(585 citation statements)

References 8 publications

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“…The 42 animals were sequenced to an average sequencing depth of 13.9-fold. Inspection of the sequencing reads alignments and the analysis of sequencing depth along chromosome 6 in three homozygous haplotype carriers using the Integrative Genomics Viewer [43] and mosdepth [44], respectively, did not reveal large sequence variants that segregate with the fertility-associated haplotype.…”

Section: A Synonymous Variant In Wdr19 Is In Linkage Disequilibrium Wmentioning

confidence: 92%

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Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Hiltpold

Niu²,

Kadri

et al. 2020

Preprint

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Cattle are uniquely suited to investigate the genetics of male reproduction disorders, as semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. Using 26,090 ejaculates of 794 Brown Swiss bulls, we analysed ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies, and bull fertility. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing between semen quality and 607,511 SNPs reveaed a QTL on bovine chromosome 6 that was associated with sperm motility (P = 2.5 x 10 -27 ), head (P = 2.0 x 10 -44 ) and tail anomalies (P = 7.2 x 10 -49 ) and insemination success (P = 9.9 x 10 -13 ). The QTL harbors a recessive allele that compromises semen quality and male fertility. We replicated the effect of the QTL on fertility (P = 7.1 x 10 -32 ) in 2481 bulls from an independent cohort of Brown Swiss bulls. The analysis of whole-genome sequencing data revealed that a synonymous variant (BTA6:58373887C>T, rs474302732) in WDR19 encoding WD repeat-containing protein 19 was in linkage disequilibrium with the fertility-associated haplotype. WD repeat-containing protein 19 is a constituent of the intraflagellar transport complex that is essential for the physiological function of motile cilia and flagella. Bioinformatic and transcription analyses showed that the BTA6:58373887 T-allele activates a cryptic splice site that eliminates three evolutionarily conserved amino acids from the WD-repeat domain, thus reducing semen quality and fertility. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases the WDR19 protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the deleterious allele has a frequency of 24 % in the Brown Swiss population. Our findings are the first to uncover a variant that controls quantitative variation in semen quality and male fertility in cattle. Author summaryMale reproductive disorders occur in many species. In cattle farming, artificial insemination is widely used. To ensure high fertilization rates, the quality of each ejaculate is recorded and the insemination success is monitored for every artificial insemination bull. We analyse semen quality and microarray-called genotypes at more than 600,000 genome-wide SNP markers in 794 bulls to identify a recessive allele that compromises semen quality and fertility. We take advantage of whole-genome sequencing to pinpoint a variant in the coding sequence of WDR19 encoding WD repeat-containing protein 19 that activates a novel exonic splice site. Our results indicate that cryptic splicing in WDR19 is associated with reduced male reproductive performance in cattle. This is the first report to reveal a variant associated with quantitative variation in bovine semen quality.

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Section: A Synonymous Variant In Wdr19 Is In Linkage Disequilibrium Wmentioning

confidence: 92%

“…Additional details on the applied variant calling and filtration approach can be found in Crysnanto et al [93]. The mosdepth software (version 0.2.2) [44] was used to extract the number of reads that covered a genomic position.…”

Section: Whole-genome Sequencing and Sequence Variant Genotypingmentioning

confidence: 99%

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Hiltpold

Niu²,

Kadri

et al. 2020

Preprint

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“…King, unpublished) with bwa-meth (Pedersen et al, 2014) Picard Tools (Broad Institute, 2019) was used to mark PCR duplicates and the properly paired alignment rate was determined with samtools (Li et al, 2009) using options -q 10, -c, -F 3840, -f 66. Genomic coverage was determined using mosdepth (Pedersen and Quinlan, 2018) with options -x and -Q 10, and a custom Python script (bed_coverage_to_x_coverage.py). Per-cytosine methylation was extracted with MethylDackel (Ryan, 2015) in two passes, first to determine the inclusion bounds based on methylation bias per read position using MethylDackel mbias, and then with MethylDackel extract.…”

Section: Whole-genome Bisulfite Sequencing and Analysismentioning

confidence: 99%

Abundant expression of maternal siRNAs is a conserved feature of seed development

Grover

Burgess

Kendall

et al. 2019

Preprint

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Small RNAs are abundant in plant reproductive tissues, especially 24-nt short interfering (si)RNAs. Most 24-nt siRNAs are dependent on RNA Pol IV and RDR2, and establish DNA methylation at thousands of genomic loci in a process called RNA-directed DNA methylation (RdDM). In Brassica rapa, RdDM is required in the maternal sporophyte for successful seed development. Here we demonstrate that a small number of siRNA loci account for over 90% of siRNA expression during B. rapa seed development. These loci exhibit unique characteristics with regard to their copy number and association with genomic features, but they resemble canonical 24-nt siRNA loci in their dependence on RNA Pol IV/RDR2 and role in RdDM. These loci are expressed in ovules before fertilization and in the seed coat, embryo, and endosperm following fertilization. We observed a similar pattern of 24-nt siRNA expression in diverse angiosperms despite rapid sequence evolution at siren loci. In the endosperm, siren siRNAs show a marked maternal bias, and siren expression in maternal sporophytic tissues is required for siren siRNA accumulation. Together these results demonstrate that seed development occurs under the influence of abundant maternal siRNAs that might be transported to, and function in, filial tissues.

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“…Reads were aligned to the GRCh38 reference genome using minimap2 (v2.14) [13] followed by structural variant calling using Sniffles (v1.0.10) [18] . The obtained read depth was assessed with mosdepth (0.2.3) [14] . The truth set of structural variants was determined using paftools based on the alignment of the HG00733 assembly to the GRCh38 reference alignment using minimap2, after splitting the diploid assembly by haplotype [13,19] .…”

Section: Methodsmentioning

confidence: 99%

“…After alignment to the human reference genome GRCh38 with minimap2 [13] , we obtained the expected read coverage of~40x, as assessed with mosdepth [14] ( Figure S1). A limitation of our analysis is that we use a fixed read length per dataset, while real long read sequencing experiments produce a long-tailed distribution.…”

Section: Introductionmentioning

confidence: 99%

Critical length in long read resequencing

Wouter

Stražišar

Rijk

2019

Preprint

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Long read sequencing has a substantial advantage for structural variant discovery and phasing of variants compared to short-read technologies, but the required and optimal read length has not been assessed. In this work, we used simulated long reads and evaluated structural variant discovery and variant phasing using current best practice bioinformatics methods. We determined that optimal discovery of structural variants from human genomes can be obtained with reads of minimally 15 kbp. Haplotyping genes entirely only reaches its optimum from reads of 100 kbp. These findings are important for the design of future long read sequencing projects.

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Mosdepth: quick coverage calculation for genomes and exomes

Cited by 834 publications

References 8 publications

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Abundant expression of maternal siRNAs is a conserved feature of seed development

Critical length in long read resequencing

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